Hypertension and insomnia frequently co-occur, yet their molecular link is unclear. Recent studies indicate that gut microbiota metabolites significantly influence neuroimmune and cardiovascular interactions. This research aimed to explore the role of these gut microbiota derived metabolites in the co-occurrence of hypertension and insomnia through an integrative network pharmacology approach. We extracted 278 gut microbial metabolites and their targets from the gutMGene database. Target prediction was performed using SEA and Swiss Target Prediction. We compiled 13,700 hypertension and 502 insomnia disease-associated targets from six databases, identifying 408 common targets. The 18 core targets were validated through PPI network analysis, KEGG pathway enrichment, and molecular docking. Ligand-target interaction stability was tested with 100 ns molecular dynamics simulations. Drug-likeness and toxicity were assessed using SwissADME and ADMETlab2.0. The PPI network analysis highlighted IL6 and PPARG as key hubs, each with 12 connections. KEGG pathway enrichment pinpointed the IL-17 signaling pathway as crucial, linking it to lipid metabolism and neuroinflammation. Molecular docking showed 3-indolepropionic acid binds strongly to IL6 (Vina score: -5.472 kcal/mol), supported by stable molecular dynamics simulations. Drug-likeness screening identified butyrate and 3-indolepropionic acid as promising, with no hepatotoxicity or cardiotoxicity. The MMTS network analysis emphasized Lacticaseibacillus paracasei as a major regulator of IL-17 signaling pathways. This study highlights the role of the microbiota-metabolite-inflammation axis in hypertension and insomnia comorbidity, suggesting IL-17 inhibition and microbial metabolite supplementation as treatments. It provides a theoretical framework and potential targets for developing gut-derived metabolite-based interventions for hypertension-insomnia comorbidity.
Ma et al. (Sun,) studied this question.